Nan Sethakorn, MD, PhD

Targeted therapies are highly effective in certain types of lung cancer. However non-cancerous cells around tumors can promote lung cancer growth. Targeted therapies do not work as well in lung cancer that has spread to bone, which occurs frequently. It is likely that multiple bone cells prevent treatments from working. We developed methods to grow lung cancer and non-cancerous cells from patients in miniaturized tissue chips to test new treatments. Using our miniaturized tissue chips, we can recreate the bone environment, aim to identify factors that promote lung cancer growth in bone, and test new treatments to combat this. We also aim to identify markers in blood to determine which patients are at risk for bone metastases before they can be detected on routine scans. These patients may benefit from earlier treatment with bone-strengthening drugs that are already known to prevent fractures from cancer that spread to bone. These results would support a future clinical trial to test this question.

Update: We have made strong progress in uncovering new pathways that may cause resistance to a type of lung cancer treatment called EGFR-TKIs in bone metastases. This treatment targets errors in the EGFR gene. We discovered that osteoclasts (bone cells) taken from patients can make EGFR-mutated non-small cell lung cancer (NSCLC) cells resistant to EGFR tyrosine kinase inhibitors (TKIs). By studying the substances released by these osteoclasts, we found several potential factors that may cause this resistance. We are now working to understand the pathways behind this effect to see if we can reverse it. These resistance-related pathways might also encourage other harmful cancer behaviors, such as invasion and immune evasion, and could apply to other types of NSCLC as well. This research could lead to new treatments that block these resistance signals and make EGFR-TKIs effective again.